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Prion protein is associated with a worse prognosis of head and neck squamous cell carcinoma

2021; Wiley; Volume: 50; Issue: 10 Linguagem: Inglês

10.1111/jop.13188

1600-0714

Eloá Mangabeira Santos, Carlos Alberto de Carvalho Fraga, Alessandra Rejane Ericsson de Oliveira Xavier, Mauro Aparecido de Sousa Xavier, Marcela Gonçalves de Souza, Sabrina Ferreira de Jesus, Alfredo Maurício Batista de Paula, Lucyana Conceição Farias, Sérgio Henrique Sousa Santos, Tiago G. Santos, Flávio H. Beraldo, André Luiz Sena Guimarães,

Cancer-related Molecular Pathways

Abstract Background Head and neck squamous cell carcinoma (HNSC) etiopathogenesis remains unclear, and the biological changes with the activation of heat shock proteins (HSPs) and prion protein (PRNP) promoted by hypoxia in HNSC are undetermined. This study investigates hypoxia's effect in lymph node metastasis by PRNP expression changes and its main partners. Methods The study combined a theoretical/cell culture study with a case‐control study. First, bioinformatics and cell culture were performed. A case‐control study was performed in a second step by comparing HNSC patients with and without lymph node metastasis. Analyses The Cancer Genome Atlas (TCGA) data source validates the theory in the global population study. Results Bioinformatics analysis suggests that hypoxia‐inducible factor‐1α (HIF1A) is associated with HSPA4, HSP90AA1 and PRNP expression. TCGA data validate the hypothesis that higher HSP90AA1, HSPA4 and PRNP are related to metastases and low survival. Herein, the cell study demonstrated that muted PRNP did not respond to hypoxia. Discussion Our results collectively provide the first evidence that PRNP promotes HNSC lymph node metastasis progression through the upregulation of HSPA4, HSP90AA1 and HIF1A. Our findings may provide a molecular basis for the promoting Role of PRNP in HNSC progression.